Implantation of pure crystalline pellets of estradiol for conception control

Greenblatt, Robert B.; Asch, Ricardo H.; Mahesh, Virendra B.; Bryner, James R.

doi:10.1016/0002-9378(77)90447-1

Cited by 29 publications

(11 citation statements)

References 9 publications

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“…The initial dose of oestradiol (Organon) inserted was usually 100 mg, the dose that has been shown to inhibit ovulation and act as a contraceptive [3]. Subsequent doses, given when symptoms began to return, were generally decreased to a maintenance of 50 mg ( Table I).…”

Section: Methodsmentioning

confidence: 98%

Management of the Premenstrual Syndrome by Subcutaneous Implants of Oestradiol

Magos

Collins

Studd

1984

Journal of Psychosomatic Obstetrics & Gynecology

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The suppression of cyclical ovarian activity by subcutaneous implants of oestradiol has been used to treat the premenstrual syndrome (PMS) in 92 patients, including 16 who also suffered from menstrual migraine. The treatment, usually with an initial dose of 100 mg oestradiol, reduced to 50 mg every 6 months, has continued for upto 7 years, with a mean duration of therapy of 2.0 years; 80% of patients have had more than one implant, and 32% have had five or more. Complete or almost complete relief of the symptoms of the PMS was reported by 84%. Previous medication was reduced or discontinued by 83%. Of the 84% where a comparison could be made with previous treatments, 93% considered implant therapy to be the most effective.Progestogen was given cyclically, usually for 7-10 days each month, to induce regular withdrawal bleeding and prevent endometrial hyperplasia. This was associated with the return of the patients' characteristic premenstrual symptoms in 45%, but to a lesser degree and for a shorter duration than prior to implant treatment.We suggest that (1) PMS is a result of unspecified cyclical biochemical changes following ovulation, (2) the symptoms can be removed by subcutaneous oestradiol implants of a sufficient dose to inhibit cyclical ovarian activity, and (3) the symptoms can be reproduced by oral progestogens.

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Section: Methodsmentioning

confidence: 98%

Management of the Premenstrual Syndrome by Subcutaneous Implants of Oestradiol

Magos

Collins

Studd

1984

Journal of Psychosomatic Obstetrics & Gynecology

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“…Many absorption routes have been studied for E2, including the percutaneous (Basdevant & De Lignieres 1980), oral (Yen et al 1975, vaginal (Rigg et al 1978, intramuscular (Sommerville 1975) and implantation pathways (Greenblatt et al 1977). Apart from one very recent paper (Burnier et al 1981), however, no description exists of absorption by the sublingual route.…”

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confidence: 97%

Post-menopausal concentrations of plasma oestradiol, oestrone, FSH and LH and of total urinary oestradiol and oestrone after a single sublingual dose of oestradiol-17β

Fiet

Hermano

Witte

et al. 1982

Acta Endocrinologica

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We report the effects of sublingual absorption of a single dose (0.5 mg) of oestradiol-17\g=b\(E2) in 8 post-menopausal women, on plasma E2 and oestrone (E1), urine elimination of total E2 + E1 and on plasma FSH and LH.The results show that sublingual absorption of E2 occurs and that plasma concentrations of E2 obtained (between 133.2 to 320 pmol/1) in this way were higher than those obtained after percutaneous absorption of a single dose (3 mg)of E2. The ratio E1/E2 in plasma is close to that of pre-menopausal women.Although synthetic forms of oestrogen are effec¬ tive in treating menopausal symptoms, they are now less commonly used because of side-effects in the liver (Kern et al. 1978) and cardiovascular system (Irey & Norris 1973; Gammal 1976), and the natural oestrogen oestradiol-I7ß (E2) is con¬ sidered preferable. Nevertheless, its concentration in the patients plasma after administration, as well as that of its chief metabolite oestrone (Ei) should both remain as close as possible to pre-menopausal physiological levels. Many absorption routes have been studied for E2, including the percutaneous (Basdevant & De Lignieres 1980), oral (Yen et al. 1975, vaginal (Rigg et al. 1978), intramuscular (Sommerville 1975) and implantation pathways (Greenblatt et al. 1977). Apart from one very recent paper (Burnier et al. 1981), however, no description exists of absorption by the sublingual route.Our aim was to determine whether E2 can be absorbed sublingually. 'Glossettes1' of E2 were administered in single doses to 8 post-menopausal women and plasma concentration of E2, E^F SH and LH were measured, in addition to the sum of the Et and E2 excreted in the urine.Finally, for purposes of comparison, 6 of the 8 women were given a percutaneous application of E2 one week after the sublingual dose and the same parameters were measured. Materials and Methods PatientsOur series was of 9 post-menopausal women, but we excluded one 70-year-old patient with very high levels of basal E2. Investigation revealed that she was using beauty creams containing oestrogen.The ages of the 8 patients studied ranged from 47 to 69 years and their mean weight was 55 kg. Six patients had experienced a natural menopause and 2 had under¬ gone hysterectomy with bilateral ovariectomy. The time elapsing between the onset of menopause and the in¬ vestigation ranged from 4 to 24 years. No patient had received oestrogen treatment during that time. None was suffering from kidney, liver or thyroid complaints or disturbed salivation. All medication was stopped during the trial. »Laboratoire Fournier, BP 130, 21004 DIJON cédex,

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“…In order to reduce the incidence of dysfunctional uterine bleeding and endometrial hyperplasia, which occurred in some of Greenblatt's patients [6,21], we extended the use of progestogen from 5 to 7 days monthly. In our series, bleeding occurred in only a few patients who did not follow orders for the proper monthly use of the progestogen.…”

Section: Commentmentioning

confidence: 99%

“…The amount of absorption is apparently a physical phenomenon depending on the surface area of the pellets exposed to the dissolving action of the tissue fluids. The rate of absorption will depend on the number of pellets that are implanted (surface area), and the duration of its effect will depend on the weight of the pellets [5,6]. The fate of an estradiol molecule that is absorbed through the subcutaneous tissue or other parenteral routes differs considerably from that of one that is absorbed enterally.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous Implantation of Pure Crystalline Estradiol Pellets for Conception Control

Oettinger

Barak²,

Oettinger‐Barak³

et al. 2005

Gynecol Obstet Invest

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Objectives: Assessment of the contraceptive effectiveness of pure estradiol pellets implanted annually under the skin, thus avoiding the ‘first passage phenomenon’ through the liver, using a modification of Emperaire and Greenblatt’s method. Study Design: 228 women wishing birth control for 1 year or more were included. 5 pellets of estradiol (25 mg each) were implanted initially. At each subsequent annual treatment, 4 pellets were implanted. Withdrawal bleeding was induced monthly with oral norethindrone acetate 5 mg taken for 7 days. Our experience encompassed 8,136 cycles, or 678 women years. The study obtained approval of the local Ethical Committee. Results: Annual continuation rates were 51 per 100 women in the second year, 65 in the third, 72 in the fourth and 84 ± 10.1 annually over the next 6 years. Through 12 years of our study, 2 accidental pregnancies occurred. The annual net cumulative pregnancy rates were 0.44 and 0.48 per 100 women at 1 and 2 years, and reduced to 0.29 at the end of 10 years. Return of fecundity after discontinuing treatment was 53% after 12 months, 81% after 24 months and 89% after 36 months. The mean estradiol levels were 1,413 ± 161 pmol/l one week following the pellet installation. The mean serum estradiol level of the 43 women who were assayed arbitrarily or a year following last insertion was 1,207 pmol/l (range 462–2,904 pmol/l); 22% had serum estradiol levels <1,000 pmol/l and 6.3% (3 women) had levels >1,750 pmol/l. A total of 28 endometrial biopsies were obtained –19 were proliferative, 6 showed slight simple hyperplasia, and three, benign cystic glandular hyperplasia. Conclusion: Subcutaneous implantation of pure estradiol pellets offers excellent birth control, has minimal untoward effects, is simple to insert and can serve as a possible alternative for conception control. It could be considered for 3 indications: for women who have completed family planning; for women in older age group (above 35 years) who are approaching the climacteric; and for women at any age, who need prolonged periods of contraception.

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Implantation of pure crystalline pellets of estradiol for conception control

Cited by 29 publications

References 9 publications

Management of the Premenstrual Syndrome by Subcutaneous Implants of Oestradiol

Management of the Premenstrual Syndrome by Subcutaneous Implants of Oestradiol

Post-menopausal concentrations of plasma oestradiol, oestrone, FSH and LH and of total urinary oestradiol and oestrone after a single sublingual dose of oestradiol-17β

Subcutaneous Implantation of Pure Crystalline Estradiol Pellets for Conception Control

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